Platelets are critical for blood clotting. However, in various human anemias, and in bone marrow transplant patients, platelets and the megakaryocytes they are derived from can drop below a critical threshold that is required to maintain normal clotting. This can require platelet transfusions that are very expensive and which place the patient at risk for infection by blood-borne pathogens (e.g. HIV, HepB and C).
Mice that lack expression of a SH2-domain-containing Inositol 5-Phosphatase (SHIP) gene exhibit increased levels of both megakaryocyte progenitors and megakaryocytes in the bone marrow and spleens. In fact, megakaryocytes, the immediate precursor of platelets, are increased in the periphery of SHIP deficient mice approximately 10-100 fold. Therefore, methods that inhibit SHIP expression, its enzymatic activity or its signaling functions could be used in human patients to temporarily increase megakaryocytes and platelet numbers during periods when their platelets drop below numbers sufficient to promote normal blood clotting. In a similar way, SHIP expression or activity could be used to increase the yield of megakaryocytes, megakaryocyte progenitors or platelets in ex vivo expansion regimens that use human growth factors.